Objective: The goal of this review is to summarize the present controversy surrounding the safety of beta 2-agonists in the treatment of asthma. This article presents a brief summary of questions and issues related to (1) increased mortality, (2) morbidity, (3) airways reactivity, and (4) tolerance.
Data sources: References are limited to the English language and extend back to the late 1960s. Articles included are based on clinical experience in humans.
Study selection: Papers were selected on the basis of being representative of the four controversial issues regarding beta 2-agonists presented in this review.
Results: Analysis of the available data regarding the use of inhaled beta 2-agonists does not support the existence of major adverse effects. Inconsistencies both within and between published reports preclude identification of a recognizable pattern of adverse effects associated with use of these drugs. The argument that beta 2-agonists, as a class, have caused an increase in asthma mortality is weak. Fenoterol alone, due to its formulation and marketing position, may have been associated with asthma deaths because it was used more frequently in patients with unstable and difficult-to-control asthma. The Canadian studies suggesting a class effect do not reconcile with negative findings around the world. Purported evidence of increased asthma morbidity associated with regular use of beta 2-agonists is unconvincing due to problems with the analyses, the small physiologic changes observed, and the lack of confirmation of loss of asthma control in other studies using similar designs. There also are no convincing data that beta 2-agonists unfavorably modulate bronchial responsiveness in patients with asthma or reduce the protection to constrictor stimuli in a clinically meaningful way.
Conclusions: beta-Agonists have been used for more than 30 years to treat and prevent asthma, yet the controversy over the safety of these drugs has surfaced only occasionally during this period. A careful review of the data should result in the conclusion that beta 2-agonists remain an appropriate and reliable treatment option for patients with asthma.